A major problem with controlling temperature both in the hyperthermia and tissue ablation ranges is the strong dependence of temperature of blood perfusion rate which can vary considerably among tumors and within a single tumor. One possible solution to this problem is to use very short heating times since the initial temperature elevation does not depend strongly upon the blood perfusion rate. In order to deliver a therapeutic thermal exposure in a short time, high temperatures (50 - 100 degrees C) have to be induced. These high temperatures require accurate delivery and control in order to avoid damage outside the target volume. At the moment focused ultrasound is the only method that can deliver such exposures in deep tissues. The research done under the first phase of this grant has established and tested the sonication parameters for inducing hyperthermia and coagulation necrosis in deep tissues. Recently, we have demonstrated a novel solution for real time monitoring and control of the focused ultrasound using online Magnetic Resonance Imaging (MRI) to visualize the temperature elevation during sonication and delineate the tissue necrosis. MRI has sufficient temporal and spatial resolution as well as temperature sensitivity for accurate delivery of the thermal exposure. The next phase of this research will concentrate on investigating high thermal exposure levels which produce protein coagulation and on developing a system for clinical tests. Phased arrays will be developed and optimized so that clinically relevant tumor volumes can be treated. The phased arrays will be optimized using computer models, phantoms and different tissues in vivo. In addition, different degrees of ultrasound induced tissue damage will be correlated with their MRI appearance; the safety and long term effects of the therapy will be studied; the optimal MRI sequence will be established; the planning and controlling software will be developed; and the hardware will be constructed. At the completion of this research project a device will be ready for testing noninvasive induction of protein coagulation as an alternative for surgery. The potential benefits of such noninvasive surgery are: First, high spatial accuracy due to high soft tissue contrast of MRI. Second, the temperature sensitivity of MR signal can be used to monitor the temperature elevation in surrounding normal tissues to increase safety. Third, low power test pulses can be used to verify the focal location prior to the high power exposure. Fourth, the recovery time, hospital stay, and risk for infection and other complications could be reduced when compared with conventional surgery. Finally, a successful implementation of such a noninvasive procedure would significantly reduce the cost of the operative procedure.